2-(4-(2-(4-benzylpiperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(4-(2-(4-benzylpiperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione
• 英文别名: 2-[[4-[2-(4-Benzylpiperazin-1-yl)ethyl]phenyl]methyl]isoindole-1,3-dione；2-[[4-[2-(4-benzylpiperazin-1-yl)ethyl]phenyl]methyl]isoindole-1,3-dione
• 化学式: C₂₈H₂₉N₃O₂
• 分子量: 439.557
• InChiKey: DQNQPTZBYUYYHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(溴甲基)苯乙酸 在 4-二甲氨基吡啶 、 dimethyl sulfide borane 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 59.0h， 生成 2-(4-(2-(4-benzylpiperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Synthesis, structure–activity relationship and biological evaluation of novel arylpiperzines as α1A/1D-AR subselective antagonists for BPH

  摘要：

  A series of novel arylpiperazine derivatives as alpha(1A/1D)-adrenergic receptors (AR) subtype selective antagonists were designed, synthesized and evaluated for their antagonistic activities towards alpha(1)-ARs (alpha(1A), alpha(1B), and alpha(1D)). Compounds 9, 12, 13, 15, 17, 18, 21, 22, 25 and 26 exerted strong antagonistic effects on alpha(1A) and/or alpha(1D) subtypes over alpha(1B) in vitro. SAR analysis indicated that chloride at the ortho-phenyl position for compound 17 was beneficial for the highest alpha(1A/D)-AR sub-selectivity. Moreover, molecular docking study of compound 17 with the homology-modeled alpha(1)-ARs (alpha(1A), alpha(1B), and alpha(1D)) structures exhibited differences of key amino resides in the docking pocket which may influence the subtype selectivity. ILE 193 of alpha(1A) was validated as the key residues for binding ligand. This work provides useful information for finding more new potential drugs in clinic in treating benign prostatic hyperplasia (BPH). (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.020

文献信息

• Synthesis, structure–activity relationship and biological evaluation of novel arylpiperzines as α1A/1D-AR subselective antagonists for BPH
  作者：Fang Xu、Hong Chen、Jingyi Xu、Xue Liang、Xuelan He、Binhao Shao、Xianqiang Sun、Bing Li、Xiaoliang Deng、Mu Yuan

  DOI：10.1016/j.bmc.2015.11.020

  日期：2015.12

  A series of novel arylpiperazine derivatives as alpha(1A/1D)-adrenergic receptors (AR) subtype selective antagonists were designed, synthesized and evaluated for their antagonistic activities towards alpha(1)-ARs (alpha(1A), alpha(1B), and alpha(1D)). Compounds 9, 12, 13, 15, 17, 18, 21, 22, 25 and 26 exerted strong antagonistic effects on alpha(1A) and/or alpha(1D) subtypes over alpha(1B) in vitro. SAR analysis indicated that chloride at the ortho-phenyl position for compound 17 was beneficial for the highest alpha(1A/D)-AR sub-selectivity. Moreover, molecular docking study of compound 17 with the homology-modeled alpha(1)-ARs (alpha(1A), alpha(1B), and alpha(1D)) structures exhibited differences of key amino resides in the docking pocket which may influence the subtype selectivity. ILE 193 of alpha(1A) was validated as the key residues for binding ligand. This work provides useful information for finding more new potential drugs in clinic in treating benign prostatic hyperplasia (BPH). (c) 2015 Elsevier Ltd. All rights reserved.